OnKure Therapeutics Announces First Patient Dosed in the Phase 1b/2 Nautilus Trial of OKI-179 in Combination with Binimetinib in Patients with Advanced NRAS-Mutated Melanoma

BOULDER, Colorado—June 2, 2022 — OnKure, Inc., a clinical-stage biopharmaceutical company discovering and developing the next generation of oncology precision medicines, today announced that the first patient has been dosed in the Phase 1b/2 Nautilus trial of OKI-179, the Company’s oral Class I histone deacetylase (HDAC) inhibitor, in combination with binimetinib (MEKTOVI®), Pfizer’s MEK inhibitor, in patients with advanced NRAS-mutated melanoma.

“We are pleased to advance the clinical development of our lead candidate, OKI-179, and for the first time, investigate its potential in combination with a MEK inhibitor," said Jennifer Diamond, M.D., Chief Medical Officer of OnKure. “The combination of HDAC inhibition with MEK inhibition is synthetically lethal in RAS-pathway mutated cancers, resulting in increased tumor regressions by inducing DNA damage that is not seen with either agent alone. Given the favorable safety and tolerability profile of OKI-179, we believe its synergistic combination with binimetinib has the potential to be an effective treatment option for patients diagnosed with this highly aggressive melanoma.”

The Phase 1b/2 Nautilus study is an open-label, dose-escalation and expansion trial designed to determine the safety and efficacy of OKI-179 combined with binimetinib in patients with NRAS-mutated melanoma. OKI-179 will be administered on a 4 days on/3 days off schedule, with binimetinib administered BID continuously. The Phase 1b portion of this study will determine the maximum tolerated dose, the dose-limiting toxicities, and the recommended Phase 2 dose (RP2D) of OKI-179 and binimetinib in patients with RAS-pathway mutated solid tumors. The Phase 2 portion of the trial is designed as a Simon’s optimal 2-stage study that will investigate the efficacy of the combination of OKI-179 and binimetinib at the RP2D in patients with previously treated NRAS-mutated melanoma. For more information about the study, please visit www.clinicaltrials.gov (NCT05340621).

About NRAS-Mutated Melanoma
NRAS is the second most common oncogenic driver in melanoma, accounting for 20% of all melanomas. Tumors bearing NRAS mutations are more aggressive and are associated with poorer patient outcomes. Despite the prevalence of NRAS mutations and the severity of the resulting disease, treatment options for NRAS-mutated melanoma remain limited, with little efficacy.

About OKI-179
OKI-179 is a novel, oral Class I histone deacetylase (HDAC) inhibitor for the potential treatment of a wide range of solid and hematological malignancies. HDAC inhibitors have shown great promise in preclinical models, however they have had little success treating solid tumors, often due to poor tolerability, inappropriate dosing regimens, poorly conceived combinations, and a lack of stratifying biomarkers. OKI-179 is designed to have improved potency, selectivity, tolerability, as well as easy combinability to overcome the historic limitations of other HDAC inhibitors.

About OnKure Therapeutics
OnKure, Inc. is a clinical-stage biopharmaceutical company focused on the discovery and development of best-in-class precision medicines that target biologically validated drivers of cancer. Using its proven structure-based drug design approach, the Company is building a robust pipeline of tumor-agnostic candidates that are designed to achieve optimal tolerability and efficacy. OnKure is currently developing its lead clinical candidate, OKI-179, an oral, selective Class I HDAC inhibitor, for the treatment of both hematological and solid tumors.

For more information, please visit www.onkuretherapeutics.com and follow us on LinkedIn and Twitter.